A common and early manifestation of aging in mammalian species is the dramatic deterioration of skeletal muscles as shown by decreased muscular efficiency, increased fatigability, and slowing of motor reactions. The working hypothesis considered here is that such aging deficits are partly due to abnormalities in "neurotrophic" functions. Thus, the long-term objective of this project is to determine whether skeletal muscle aging involves a decline in the nerve's "trophic" capacity and/or in the muscles' response to "neurotrophic" influences. These possibilities will be explored by evaluating the "trophically-controlled" and "neurotransmission-related" molecular forms of acetylcholinesterase (AChE). Emphasis will be placed on the 16S AChE form because with advancing age its activity decays much earlier than that of other AChE forms and it is thought to represent the physiologically functional enzyme at the motor endplate. Specific aims include studies on: (I) Aging of gracilis muscles from Fisher 344 rats with regard to changes in the formation and subcellular distribution of AChE and their possible relationship with alterations in effective neuromuscular transmission, other transmission-associated molecules, and/or muscle fiber type and morphology. (II) The effects of denervation on muscle 16S AChe subcellular pools; the influence of soluble nerve extracts from young adult rats on the formation of 16S AChE in endplate regions of organ cultured muscles from rats of different ages; and, the action of soluble nerve extracts from rats of different ages on the formation of 16S AChE in endplate regions of organ cultured muscles from young adult rats. Results from this project will break new ground by providing information on the mechanism(s) and physiological relevance of age-related changes in AChE forms in reference to other molecular, electrophysiological and morphological neuromuscular alterations. This information is important to determine the possible contribution of AChE form changes to the functional deficits observed in aging akeletal muscles and to elucidate how these events can be modified.